POS0705 DILEMMA OF BELIMUMAB THERAPY (DIS) CONTINUATION DURING PREGNANCY: RESULTS OF A RETROSPECTIVE STUDY IN EUDRAVIGILANCE
Authors: N. Ghalandari, H. J. M. J. Crijns, R. Dolhain, J. Hazes, E. Van Puijenbroek
Journal: Annals of the Rheumatic Diseases (2022)

Background Active systemic lupus erythematosus (SLE) and nephritis due to SLE contribute to poor pregnancy outcomes. (1, 2) A meta-analysis has shown a relative risk of 1.51 for miscarriage in SLE patients compared to women without SLE. (3) The risk is even higher if the disease is active during pregnancy (around 3-fold increase in pregnancy loss). (4) Corticosteroids, azathioprine, hydroxychloroquine, ciclosporine and tacrolimus are considered safe treatments. (5) However, these treatment options may still not be sufficient in patients poorly responsive to conventional therapies or patients who suffer from nephritis. (6) The only biologic authorized for SLE up to this date, belimumab, is currently not recommended for use during pregnancy due to lack of data. Provided that the health of the child begins with the health of the mother, pregnant patients, face the dilemma of cessation or continuation of belimumab. If belimumab is stopped there will be a risk of SLE flare and its consequences for mother and foetus. Continuation is also not optimal because the lack of knowledge on safety for use during pregnancy. Objectives To compare the reported foetal outcomes in SLE patients who stopped scheduled belimumab within the first trimester (group A) and who continued scheduled belimumab during the first trimester or thereafter (group B). Methods All belimumab-exposed pregnancy-related reports, were extracted from the EudraVigilance (EV) database until March 11th 2021. After case review, repeated cases, uninformative reports, non-medical elective abortions and foetal chromosomal abnormalities were excluded. Included pregnancies were divided into two groups (group A and B, as described above). Foetal outcomes were divided into live birth or foetal death (due to miscarriage or still birth) and were compared between both groups. Furthermore, neonatal outcomes, such as reporting rates of pre-term birth, low birth weight and major congenital malformations (CMs) were compared. Results No statistical difference in foetal death was observed between group A and B (reporting rates: 46.4% and 52.4%, respectively; p-value&gt;0.05). Occurrence of major CMs, pre-term birth and low birth weight was higher - though not statistically different- in group A (Table 1). Table 1. Neonatal characteristics of live born children (including twin pregnancies) Live births Stopped (group A); (n=37) Continued (group B); (n =10) Total; (n=47) Gestational age at birth, median (IQR), weeks 37.1 (35.5, 40.0) 38.2 (36.4, 39.1) 37.6 (36.0, 39.4 ) Weight, median (IQR), grams 2749 (2268, 3200) 2975 (2700, 3175) 2835 (2406-3175 ) Preterm birth*; n (%) 16 (43.2) 4 (40.0) 20 (42.5 ) Low birth weight*; n (%) 9 (24.3) 0 (0.0) 9 (19.4 ) Conclusion Based on our data belimumab continuation during first trimester or thereafter does not result in higher reporting of foetal death. Therefore, continuation might be even preferable if the pregnancy is already exposed to belimumab. Since the analysis is based on spontaneous reports / retrospective data, additional studies are needed to confirm the results. References [1]Bremme K, Honkanen S, Gunnarsson I, Chaireti R. The presence of lupus nephritis additionally increases the risk of preeclampsia among pregnant women with systemic lupus erythematosus. Lupus. 2021;30(7):1031-8. [2]Østensen M, Cetin I. Autoimmune connective tissue diseases. Best Pract Res Clin Obstet Gynaecol. 2015;29(5):658-70. [3]Bundhun PK, Soogund MZ, Huang F. Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: A meta-analysis of studies published between years 2001-2016. J Autoimmun. 2017;79:17-27. [4]Clowse MEB, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis &amp; Rheumatism. 2005;52(2):514-21. [5]Moroni G, Ponticelli C. Pregnancy in women with systemic lupus erythematosus (SLE). Eur J Intern Med. 2016;32:7-12. [6]Goldblatt F, Isenberg DA. New therapies for systemic lupus erythematosus. Clin Exp Immunol. 2005;140(2):205-12. Acknowledgements We would like to thank C. Zaccaria and L. Piccolo for their contributions to access and interpreting data from EudraVigilance database. The views expressed in this article are the personal views of the author(s) and may not be understood or quoted as being made on behalf of or reflecting the position of the regulatory agency/agencies or organizations with which the author(s) is/are employed/affiliated. Disclosure of Interests Nafise Ghalandari: None declared, Hubertina Johanna Maria Josephina Crijns: None declared, Radboud Dolhain Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Lilly, Grant/research support from: unrestricted research grants from: Dutch Arthritis Association, UCB Pharma, Galapagos, Johanna Hazes: None declared, Eugène van Puijenbroek: None declared